Anterior insular cortex is necessary for empathetic pain perception

Abstract

Empathy refers to the ability to perceive and share another person's affective state. Much neuroimaging evidence suggests that observing others' suffering and pain elicits activations of the anterior insular and the anterior cingulate cortices associated with subjective empathetic responses in the observer. However, these observations do not provide causal evidence for the respective roles of anterior insular and anterior cingulate cortices in empathetic pain. Therefore, whether these regions are 'necessary' for empathetic pain remains unknown. Herein, we examined the perception of others' pain in patients with anterior insular cortex or anterior cingulate cortex lesions whose locations matched with the anterior insular cortex or anterior cingulate cortex clusters identified by a meta-analysis on neuroimaging studies of empathetic pain perception. Patients with focal anterior insular cortex lesions displayed decreased discrimination accuracy and prolonged reaction time when processing others' pain explicitly and lacked a typical interference effect of empathetic pain on the performance of a pain-irrelevant task. In contrast, these deficits were not observed in patients with anterior cingulate cortex lesions. These findings reveal that only discrete anterior insular cortex lesions, but not anterior cingulate cortex lesions, result in deficits in explicit and implicit pain perception, supporting a critical role of anterior insular cortex in empathetic pain processing. Our findings have implications for a wide range of neuropsychiatric illnesses characterized by prominent deficits in higher-level social functioning.

Figure 1

(A) Common brain activation related to empathetic pain perception as revealed by a meta-analysis on 28 functional MRI studies on empathetic pain (false-discovery rate P < 0.05 and cluster size > 240 mm³). Anterior insular and anterior cingulate cortices showed the most consistent activation among all 28 studies. (B) Reconstruction of anterior insular cortex lesions of three patients and (C) reconstruction of anterior cingulate cortex lesions of another three patients. Lesions were mapped on the same hemisphere to show degree of overlap. The brain template used in (B) and (C) was created by a neurologist (R.T.K.) and its reference line is tilted 12 degrees from the anterior commissure—posterior commissure plane. Red colour indicates 100% overlap.

Figure 2

Sample stimuli of the experimental stimulus set of 216 digital colour photographs showing another person’s left or right hand/foot in painful or non-painful situations. Subjects were instructed to choose between ‘non-painful’ and ‘painful’ for the task pain and ‘left’ and ‘right’ for the task laterality through button press within a time window of 4 ms (2.5 ms of stimulus display and 1.5 s of fixation).

Figure 3

Behavioural performance on task pain (TP). (A) Patients with anterior insular cortex (AIC) lesions (P < 0.05), but not anterior cingulate cortex patients (P > 0.05), had significantly smaller d′ compared with neurologically intact controls and brain-damaged controls, indicating impaired discrimination accuracy to empathetic pain in anterior insular cortex patients. (B) Neither patients with anterior insular cortex lesions nor those with anterior cingulate cortex lesions showed any significant alternation in decision bias indexed by β during task pain (P > 0.05). (C) Neither patients with anterior insular cortex lesions nor anterior cingulate cortex lesions showed any significant alternation in overall reaction time (RT) [(RT_TP-pain + RT_{TP-no pain})/2] (P > 0.05). (D) Patients with anterior insular cortex lesions (P < 0.01 versus neurologically intact controls and P < 0.05 versus brain-damaged controls), but not those with anterior cingulate cortex lesions (P > 0.05), had greater cost of pain (RT_TL-pain – RT_{TL-no pain}). Error bar represents 95% confidence interval (CI). Statistical inference was not based on 95% confidence interval but on the bootstrapping method. All reaction times were calculated based on correct trials only. *P < 0.05; **P < 0.01.

Figure 4

Behavioural performance on task laterality (TL). (A) Patients with anterior insular cortex lesions (P < 0.01), but not those with anterior cingulate cortex lesion patients (P > 0.05), lacked the normal interference effect of pain on laterality discriminability. (B) Neither patients with anterior insular cortex lesions nor those with anterior cingulate cortex lesions showed significant difference in interference effect of pain on task laterality decision bias (P > 0.05). (C) Neither the anterior insular cortex lesions nor the anterior cingulate cortex lesions showed any significant alternation during laterality judgment in overall reaction time (RT) of task laterality (TL) [(RT_TL-pain + RT_{TL-no pain})/2] (P > 0.05). (D) Neither patients with anterior insular cortex lesions nor those with anterior cingulate cortex lesions showed significant differences in RT cost of pain during TL (RT_TL-pain − RT_{TL-no pain}) (P > 0.05). Error bar represents 95% confidence interval. Statistical inference was not based on 95% confidence interval but on the bootstrapping method. All RTs were calculated based on correct trials only. **P < 0.01.